Abstract
Metalloporphyrins are structural analogs of heme and their potential use in the management of neonatal hyperbilirubinemia has been the subject of considerable research for more than three decades. The pharmacological basis for using this class of compounds to control bilirubin levels is the targeted blockade of bilirubin production through the competitive inhibition of heme oxygenase (HO), the rate-limiting enzyme in the bilirubin production pathway. Ongoing research continues in the pursuit of identifying ideal metalloporphyrins, which are safe and effective, by defining therapeutic windows and targeted interventions for the treatment of excessive neonatal hyperbilirubinemia.
Highlights
Metalloporphyrins (Mps) and their potential use in the management of neonatal hyperbilirubinemia has been the subject of considerable research for more than three decades
Not orally absorbable Plasma bilirubin declined Biliary cirrhosis → 7–25% Gilbert syndrome → 29–43% Plasma bilirubin declined 38% for at least 4 days t1/2 ≈ 3.4 h Heme excreted in the bile Moderated postnatal plasma bilirubin increase Diminished intensity of hyperbilirubinemia Decreased phototherapy use t1/2 of SnPP in term babies different from adults: t1/2 ≈ 1.6 h Plasma bilirubin declined Biliary cirrhosis → 20% Hemochromatosis → 32% Decrease in biliary bilirubin t1/2 ≈ 3.4 h Heme excreted in the bile Pharmacokinetics Log-linear clearance t1/2 = 3.8 h (i.v.) Excretion: urinary and fecal
Reduced mean peak incremental plasma bilirubin levels by 41% Reduction was equal for control and SnMP groups Phototherapy requirement decreased by 76% compared to control subjects given 6-μmol/kg body weight (BW) Effectively controlled hyperbilirubinemia and was superior to phototherapy in the majority of cases
Summary
Metalloporphyrins (Mps) and their potential use in the management of neonatal hyperbilirubinemia has been the subject of considerable research for more than three decades. Since SnMP has been shown to be at least 10-fold more potent than SnPP in inhibiting HO activity (Drummond et al, 1987), clinical studies were pursued with the expectation that its high potency would allow for its use at much lower doses, and its photosensitizing effects would be minimized or maybe even eliminated. In spite of this rationale, SnMP was used in a www.frontiersin.org. Gross histology of livers, spleens, and kidneys showed evidence of infarction (Cornelius and Rodgers, 1984)
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